Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell suppressive activity

Kiavash Movahedi, Martin Guilliams, Jan Van Den Bossche, Rafael Van Den Bergh, Conny Gysemans, Alain Beschin, Patrick De Baetselier, Jo A. Van Ginderachter

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

The induction of CD11b +Gr-1 + myeloid-derived suppressor cells (MDSCs) is an important immune-evading mechanism used by tumors. However, the exact nature and function of MDSCs remain elusive, especially because they constitute a heterogeneous population that has not yet been clearly defined. Here, we identified 2 distinct MDSC subtractions with clear morphologic, molecular, and functional differences. These fractions consisted of either mononuclear cells (MO-MDSCs), resembling inflammatory monocytes, or low-density polymorphonuclear cells (PMN-MDSCs), akin to immature neutrophils. Interestingly, both MO-MDSCs and PMN-MDSCs suppressed antigen-specific T-cell responses, albeit using distinct effector molecules and signaling pathways. Blocking IFN-7 or disrupting STAT1 partially impaired suppression by MO-MDSCs, for which nitric oxide (NO) was one of the mediators. In contrast, while IFN-γ was strictly required for the suppressor function of PMN-MDSCs, this did not rely on STAT1 signaling or NO production. Finally, MO-MDSCs were shown to be potential precursors of highly antiproliferative NO-producing mature macrophages. However, distinct tumors differentially regulated this inherent MO-MDSC differentiation program, indicating that this phenomenon was tumor driven. Overall, our data refine tumor-induced MDSC functions by uncovering mechanistically distinct MDSC subpopulations, potentially relevant for MDSC-targeted thera-pies. © 2008 by The American Society of Hematology.
Original languageEnglish
Pages (from-to)4233-4244
Number of pages12
JournalBlood
Volume111
Issue number8
DOIs
Publication statusPublished - 15 Apr 2008

Cite this

Movahedi, K., Guilliams, M., Van Den Bossche, J., Van Den Bergh, R., Gysemans, C., Beschin, A., ... Van Ginderachter, J. A. (2008). Identification of discrete tumor-induced myeloid-derived suppressor cell subpopulations with distinct T cell suppressive activity. Blood, 111(8), 4233-4244. https://doi.org/10.1182/blood-2007-07-099226